Crohn's disease and ulcerative colitis are chronic inflammatory diseases of the large intestine of unknown etiology which are collectively known as Inflammatory Bowel Disease (IBD). The lesions of IBD are infiltrated with lymphocytes, plasma cells, and macrophages, implicating the immune system in disease pathogenesis although the exact immunological mechanisms involved remain unknown. The working hypothesis of this proposal is that a disorder of immunoregulation in the intestine might be the basic underlying defect in the pathogenesis of IBD. Considering the complex variety of antigens to which gut lymphoid tissues are continually exposed, it seems likely that immunoregulation must play an important role in limiting the immune response in the intestine; a defect in this immunoregulation might well lead to unrestrained responses and chronic inflammation. In previous studies we have found evidence of abnormal immunoregulation in IBD: many patrients with Crohn's disease have a circulating suppressor T cell in their peripheral blood which is a potent inhibitor of immunoglobulin synthesis. The studies proposed here are designed to examine immunoregulatory properties of T cells isolated from the lamina propria (LP) of surgically resected intestine of patients with IBD and of patients of other condictions. The specific objectives of the proposal are: 1) to assess T cell-B cell regulation by measuring the ability of LP-T cell and LP-T subsets to regulate immunoglobulin synthesis in vitro. 2) To assess T cell-T cell regulation by measuring the capabity of LP-T cells to produce and to respond to the soluble mediator interleukin 2 (IL-2). 3) To define the interactions between these two levels of regulation by determining the effects of IL-2 mediated T cell-T cell regulation on the T cell subset which regulates immunoglobulin syntesis by B cells.